Phase II Study of Alendronate Sodium in Children With High-Turnover Idiopathic Juvenile Osteoporosis

PROTOCOL OUTLINE:

Patients receive oral alendronate sodium weekly for 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.

Eligibility Criteria:

• 5-14 years of age
• Weight 20 kg or greater
• History of one or more atraumatic fracture
• Sexual development no greater than Tanner II
• Osteoporosis by DXA (Diagnosis of high-turnover osteoporosis with no underlying cause (e.g., malignancy, hyperthyroidism, hyperparathyroidism, or vitamin D intoxication)

Inclusion criteria

• Male and female children with a history of one or more atraumatic fractures, or evidence of one or more compression fractures on radiographs of the spine (reduction of >20%).
• Bone mineral density by DXA at 2 standard deviations (SD) below normal mean for age (Z-score at least 2 SD below normal mean at the lumbar spine or hip)
• Parental consent (and patient assent after age 12 years) to participate in the study.
• Sexual development at Tanner stage II or less (Prepubertal stage)
• Weight 20kg and more

Exclusion criteria

• History of severe gastritis or reflux
• Marked kyphoscoliosis or inability to sit or stand for at least 30 minutes.
• Abnormalities of the esophagus that delay emptying (e.g., strictures or achalasia)
• Hypersensitivity to bisphosphonates
• Uncorrected hypocalcemia
• History of gastric or duodenal ulcers
• Renal dysfunction as indicated by serum Creatinine greater than 1.5 mg/dL
• Liver dysfunction as indicated by serum SGPT greater than 2 times upper limit of normal for age or serum total bilirubin greater than 2.0 mg/dL
• Diagnosis of osteogenesis imperfecta (including family history) or blue sclerae or deafness
• Diagnosis of active rickets, osteomalacia, or bone alkaline phosphatase > 2 times normal for age
• Severe gastritis or reflux
• Pregnancy
• Anorexia Nervosa

• Prior/Concurrent Therapy-
• Prior course of prednisone allowed
• No concurrent prednisone except inhaled steroids
• No concurrent high-dose glucocorticoids
• No concurrent salmon calcitonin
• No other concurrent bisphosphonates
• No concurrent long-term anti-seizure medication